Graphene nanoplatelets (GNPs) offer promising properties for neural interface applications, particularly in intracranial direct current (DC) stimulation, due to their high charge injection capacity, flexibility, and biocompatibility. In this study, we comprehensively evaluate the biological and functional performance of GNP-based electrodes for acute and chronic cortical stimulation and recording. GNP electrodes were fabricated via screen-printing on flexible polyimide substrates. They were assessed for cytotoxicity using RAW 264.7 macrophage cell lines and primary hippocampal cultures, showing no evidence of cell death or toxicity. Long-term implantation in non-human primates (50 days) revealed no signs of infection, inflammation, or cortical damage, supporting the biostability of the material. Magnetic resonance imaging confirmed that GNPs produce no imaging artifacts, affirming their compatibility with standard neuroimaging protocols. Functionally, epidural DC stimulation using GNP electrodes modulated neuronal firing rates in the auditory cortex in a polarity-dependent manner, consistent with classical effects of DC stimulation. Furthermore, the same electrodes reliably recorded auditory-evoked potentials, demonstrating dual functionality for stimulation and recording. These findings position screen-printed GNP electrodes as safe, versatile, and effective tools for neurophysiological applications, and highlight their potential for future use in translational neuroscience and neurotherapeutic settings.

While it is well established that sensory cortical regions traditionally thought to be unimodal can be activated by stimuli from modalities other than the dominant one, functions of such foreign-modal activations are still not clear. Here we show that visual activations in early auditory cortex can be related to whether or not the monkeys engaged in audio-visual tasks, to the time when the monkeys reacted to the visual component of such tasks, and to the correctness of the monkeys’ response to the auditory component of such tasks. These relationships between visual activations and behavior suggest that auditory cortex can be recruited for visually-guided behavior and that visual activations can prime auditory cortex such that it is prepared for processing future sounds. Our study thus provides evidence that foreign-modal activations in sensory cortex can contribute to a subject’s ability to perform tasks on stimuli from foreign and dominant modalities.

This study aims to investigate whether the position of the eyes affects the neuronal activity in auditory cortex in a condition in which not the active control of eye position but the execution of hand movements was required relative to stimuli. Two monkeys were trained to perform audio-visual tasks in which they had to use their hand to respond to both the visual and the auditory stimuli to earn a reward. We recorded the spiking activity and the local field potentials from the core fields of auditory cortex, along with the eye position of the monkeys while they performed the tasks. We found that both the spiking activity and the local field potentials did not significantly vary with the eye position. This was the case both during the presentation of sounds and during other periods of the tasks. Our results indicate that eye position did not affect the neuronal activity in auditory cortex during the audio-visual tasks. Our results, together with the previous finding that eye position affects the neuronal activity in auditory cortex during eye fixation tasks, suggest that the presence of eye position effects in auditory cortex depends on the specific behavior a subject has to exhibit to obtain a reward.

Adaptation is the attenuation of a neuronal response when a stimulus is repeatedly presented. The phenomenon has been linked to sensory memory, but its exact neuronal mechanisms are under debate. One defining feature of adaptation is its lifetime, that is, the timespan over which the attenuating effect of previous stimulation persists. This can be revealed by varying the stimulus-onset interval (SOI) of the repeated stimulus. As SOI is increased, the peak amplitude of the response grows before saturating at large SOIs. The rate of this growth can be quantified and used as an estimate of adaptation lifetime. Here, we studied whether adaptation lifetime varies across the left and the right auditory cortex of the human brain. Event-related fields of whole-head magnetoencephalograms (MEG) were measured in 14 subjects during binaural presentation of pure tone stimuli. To make statistical inferences on the single-subject level, additional event-related fields were generated by resampling the original single-trial data via bootstrapping. For each hemisphere and SOI, the peak amplitude of the N1m response was then derived from both original and bootstrap-based data sets. Finally, the N1m-peak amplitudes were used for deriving subject- and hemisphere-specific estimates of adaptation lifetime. Comparing subject-specific adaptation lifetime across hemispheres, we found a significant difference, with longer adaptation lifetimes in the left than in the right auditory cortex (p = 0.004). This difference might have a functional relevance in the context of temporal binding of auditory stimuli, leading to larger integration time windows in the left than in the right hemisphere.

Pupil dilation in response to unexpected stimuli has been well documented in human as well as in non-human primates; however, this phenomenon has not been systematically compared between the species. This analogy is also crucial for the role of non-human primates as an animal model to investigate neural mechanisms underlying the processing of unexpected stimuli and their evoked pupil dilation response. To assess this qualitatively, we used an auditory oddball paradigm in which we presented subjects a sequence of the same sounds followed by occasional deviants while we measured their evoked pupil dilation response (PDR). We used deviants (a frequency deviant, a pink noise burst, a monkey vocalization and a whistle sound) which differed in the spectral composition and in their ability to induce arousal from the standard. Most deviants elicited a significant pupil dilation in both species with decreased peak latency and increased peak amplitude in monkeys compared to humans. A temporal Principal Component Analysis (PCA) revealed two components underlying the PDRs in both species. The early component is likely associated to the parasympathetic nervous system and the late component to the sympathetic nervous system, respectively. Taken together, the present study demonstrates a qualitative similarity between PDRs to unexpected auditory stimuli in macaque and human subjects suggesting that macaques can be a suitable model for investigating the neuronal bases of pupil dilation. However, the quantitative differences in PDRs between species need to be investigated in further comparative studies.

Behavioral flexibility allows animals to cope with changing situations, for example, to execute different actions to the same stimulus to achieve specific goals in different situations. The selection of the appropriate action in a given situation hinges on the previously learned associations between stimuli, actions, and outcomes. We showed in our recent study that early auditory cortex of nonhuman primates contributes to the selection of the actions to sounds by representing the associations between sounds and actions. That is, neurons in auditory cortex respond differently to a given sound when it signals different actions that are required to obtain a reward. Here, using the same monkey and the same tasks, we investigated whether the ventrolateral part of prefrontal cortex also represents such audiomotor associations as well as whether and how these representations differ from those in auditory cortex. Mirroring auditory cortex, neuronal responses to a given sound in prefrontal cortex changed with audiomotor associations, and the neuronal responses were largest when the sound signaled a no-go response. These findings suggest that prefrontal cortex also represents audiomotor associations and thus contributes to the selection of the actions to sounds during goal-directed behavior. The neuronal activity related to audiomotor associations started later in prefrontal cortex than in auditory cortex, suggesting that the representations in prefrontal cortex may originate in auditory cortex or in earlier stages of the auditory system.

The current study aimed to resolve some of the inconsistencies in the literature on which mental processes affect auditory cortical activity. To this end, we studied auditory cortical firing in four monkeys with different experience while they were involved in six conditions with different arrangements of the task components sound, motor action, and water reward. Firing rates changed most strongly when a sound-only condition was compared to a condition in which sound was paired with water. Additional smaller changes occurred in more complex conditions in which the monkeys received water for motor actions before or after sounds. Our findings suggest that auditory cortex is most strongly modulated by the subjects’ level of arousal, thus by a psychological concept related to motor activity triggered by reinforcers and to readiness for operant behavior. Our findings also suggest that auditory cortex is involved in associative and emotional functions, but not in agency and cognitive effort.

Possible risks stemming from the employment of novel, micrometer-thin printed electrodes for direct current neural stimulation are discussed. To assess those risks, electrochemical methods are used, including cyclic voltammetry, square-wave voltammetry, and electrochemical impedance spectroscopy. Experiments were conducted in non-deoxidized phosphate-buffered saline to better emulate living organism conditions. Since preliminary results obtained have shown unexpected oxidation peaks in 0-0.4 V potential range, the source of those was further investigated. Hypothesized redox activity of printing paste components was disproven, supporting further development of proposed fabrication technology of stimulating electrodes. Finally, partial permeability and resulting electrochemical activity of underlying silver-based printed layers of the device were pointed as the source of potential tissue irritation or damage. Employing this information, electrodes with corrected design were investigated, yielding no undesired redox processes.

An individual may need to take different actions to the same stimulus in different situations to achieve a given goal. The selection of the appropriate action hinges on the previously learned associations between stimuli, actions, and outcomes in the situations. Here, using a go/no-go paradigm and a symmetrical reward, we show that early auditory cortex of nonhuman primates represents such associations, in both the spiking activity and the local field potentials. Sound-evoked neuronal responses changed with sensorimotor associations shortly after sound onset, and the neuronal responses were largest when the sound signaled that a no-go response was required in a trial to obtain a reward. Our findings suggest that association processes take place in the auditory system and do not necessarily rely on association cortex. Thus, auditory cortex may contribute to a rapid selection of the appropriate motor responses to sounds during goal-directed behavior.

Multisensory integration in primary auditory (A1), visual (V1), and somatosensory cortex (S1) is substantially mediated by their direct interconnections and by thalamic inputs across the sensory modalities. We have previously shown in rodents (Mongolian gerbils) that during postnatal development, the anatomical and functional strengths of these crossmodal and also of sensory matched connections are determined by early auditory, somatosensory, and visual experience. Because supragranular layer III pyramidal neurons are major targets of corticocortical and thalamocortical connections, we investigated in this follow-up study how the loss of early sensory experience changes their dendritic morphology. Gerbils were sensory deprived early in development by either bilateral sciatic nerve transection at postnatal day (P) 5, ototoxic inner hair cell damage at P10, or eye enucleation at P10. Sholl and branch order analyses of Golgi-stained layer III pyramidal neurons at P28, which demarcates the end of the sensory critical period in this species, revealed that visual and somatosensory deprivation leads to a general increase of apical and basal dendritic branching in A1, V1, and S1. In contrast, dendritic branching, particularly of apical dendrites, decreased in all three areas following auditory deprivation. Generally, the number of spines, and consequently spine density, along the apical and basal dendrites decreased in both sensory deprived and non-deprived cortical areas. Therefore, we conclude that the loss of early sensory experience induces a refinement of corticocortical crossmodal and other cortical and thalamic connections by pruning of dendritic spines at the end of the critical period. Based on present and previous own results and on findings from the literature, we propose a scenario for multisensory development following early sensory loss.

The aim of this work is to test and evaluate Poly -(3,4-ethylenedioxythiophene) - poly (styrenesulfonate), simply known by the abbreviation PEDOT:PSS as a possible low cost and transparent electrically conducting polymer for the fabrication of magnetic resonance imaging (MRI) compatible brain stimulation electrodes. During the preliminary testing, the fabricated PEDOT:PSS structures with Polyimide as base layer created no artefacts under MR as well as X-Ray imaging. Additionally, as the thickness of the tested PEDOT:PSS structure was increased from 390nm to approximately 5.80μm by depositing additional material layers, the measured average electrical resistance decreased from 184KΩ to 25.37KΩ.The conventional metal-based electrodes hinder the use of MR or optical imaging during electrophysiological neuroscientific investigations of the brain. Therefore, a hybrid brain stimulation cum recording electrode array fabricated using polyimide as base material and PEDOT:PSS as the transparent electrically conducting material opens the possibility of electrically stimulating brain while simultaneously reaping the benefits of the MR imaging or the optical imaging (e.g. calcium imaging, two-photon microscopy, etc.).

Auditory perception is improved when stimuli are predictable, and this effect is evident in a modulation of the activity of neurons in the auditory cortex as shown previously. Human listeners can better predict the presence of duration deviants embedded in stimulus streams with fixed interonset interval (isochrony) and repeated duration pattern (regularity), and neurons in the auditory cortex of macaque monkeys have stronger sustained responses in the 60–140 ms post‐stimulus time window under these conditions. Subsequently, the question has arisen whether isochrony or regularity in the sensory input contributed to the enhancement of the neuronal and behavioural responses. Therefore, we varied the two factors isochrony and regularity independently and measured the ability of human subjects to detect deviants embedded in these sequences as well as measuring the responses of neurons the primary auditory cortex of macaque monkeys during presentations of the sequences. The performance of humans in detecting deviants was significantly increased by regularity. Isochrony enhanced detection only in the presence of the regularity cue. In monkeys, regularity increased the sustained component of neuronal tone responses in auditory cortex while isochrony had no consistent effect. Although both regularity and isochrony can be considered as parameters that would make a sequence of sounds more predictable, our results from the human and monkey experiments converge in that regularity has a greater influence on behavioural performance and neuronal responses.

This study finds a neuronal correlate of auditory perceptual streaming in the primary auditory cortex for sequences of tone complexes that have the same amplitude spectrum but a different phase spectrum. Our finding is based on microelectrode recordings of multiunit activity from 270 cortical sites in three awake macaque monkeys. The monkeys were presented with repeated sequences of a tone triplet that consisted of an A tone, a B tone, another A tone and then a pause. The A and B tones were composed of unresolved harmonics formed by adding the harmonics in cosine phase, in alternating phase, or in random phase. A previous psychophysical study on humans revealed that when the A and B tones are similar, humans integrate them into a single auditory stream; when the A and B tones are dissimilar, humans segregate them into separate auditory streams. We found that the similarity of neuronal rate responses to the triplets was highest when all A and B tones had cosine phase. Similarity was intermediate when the A tones had cosine phase and the B tones had alternating phase. Similarity was lowest when the A tones had cosine phase and the B tones had random phase. The present study corroborates and extends previous reports, showing similar correspondences between neuronal activity in the primary auditory cortex and auditory streaming of sound sequences. It also is consistent with Fishman’s population separation model of auditory streaming.

This study tested the hypothesis that spiking activity in the primary auditory cortex of monkeys is related to auditory stream formation. Evidence for this hypothesis was previously obtained in animals that were passively exposed to stimuli and in which differences in the streaming percept were confounded with differences between the stimuli. In this study, monkeys performed an operant task on sequences that were composed of light flashes and tones. The tones alternated between a high and a low frequency and could be perceived either as one auditory stream or two auditory streams. The flashes promoted either a one-stream percept or a two-stream percept. Comparison of different types of sequences revealed that the neuronal responses to the alternating tones were more similar when the flashes promoted auditory stream integration, and were more dissimilar when the flashes promoted auditory stream segregation. Thus our findings show that the spiking activity in the monkey primary auditory cortex is related to auditory stream formation.

Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T, provides an enhanced signal-to-noise ratio and has led to unprecedented high-resolution anatomic images and brain activation maps. Although a variety of radio frequency (RF) coil architectures have been developed for imaging at UHF conditions, they usually are specialized for small volumes of interests (VoI). So far, whole-body coil resonators are not available for commercial UHF human whole-body MRI systems. The goal of the present study was the development and validation of a transmit and receive system for large VoIs that operates at a 7 T human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting of several ring antennas was developed, since it allows for the imaging of extended VoIs. Furthermore, the MRAS not only requires lower intensities of the irradiated RF energy, but also provides a more confined and focused injection of excitation energy on selected body parts. The MRAS consisted of several antennas with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the rings was freely adjustable. Conformal resonant right-/left-handed metamaterial was used for each ring antenna with two quadrature feeding ports for RF power. The system was successfully implemented and demonstrated with both a silicone oil and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body images of a crab-eating macaque. The potential for future neuroimaging applications was demonstrated by the acquired high-resolution anatomic images of the macaque's head. Phantom and in vivo measurements of crab-eating macaques provided high-resolution images with large VoIs up to 40 cm in xy-direction and 45 cm in z-direction. The results of this work demonstrate the feasibility of the MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial potential for MR imaging of larger volumes at 7 T UHF. This new technique may provide new diagnostic potential in spatially extended pathologies such as searching for spread-out tumor metastases or monitoring systemic inflammatory processes.

We address the question of whether the auditory cortex of the left and right hemisphere and the auditory thalamus are differently involved in the performance of cognitive tasks. To understand these differences on the level of single neurons we compared neuronal firing in the primary and posterior auditory cortex of the two hemispheres and in the medial geniculate body in monkeys while subjects categorized pitch relationships in tone sequences. In contrast to earlier findings in imaging studies performed on humans, we found little difference between the three brain regions in terms of the category-specificity of their neuronal responses, of tonic firing related to task components, and of decision-related firing. The differences between the results in humans and monkeys may result from the type of neuronal activity considered and how it was analyzed, from the auditory cortical fields studied, or from fundamental differences between these species.

Working memory is the cognitive capacity of short-term storage of information for goal-directed behaviors. Where and how this capacity is implemented in the brain are unresolved questions. We show that auditory cortex stores information by persistent changes of neural activity. We separated activity related to working memory from activity related to other mental processes by having humans and monkeys perform different tasks with varying working memory demands on the same sound sequences. Working memory was reflected in the spiking activity of individual neurons in auditory cortex and in the activity of neuronal populations, that is, in local field potentials and magnetic fields. Our results provide direct support for the idea that temporary storage of information recruits the same brain areas that also process the information. Because similar activity was observed in the two species, the cellular bases of some auditory working memory processes in humans can be studied in monkeys.

Working memory denotes the ability to retain stimuli in mind that are no longer physically present and to perform mental operations on them. Electro- and magnetoencephalography allow investigating the short-term maintenance of acoustic stimuli at a high temporal resolution. Studies investigating working memory for non-spatial and spatial auditory information have suggested differential roles of regions along the putative auditory ventral and dorsal streams, respectively, in the processing of the different sound properties. Analyses of event-related potentials have shown sustained, memory load-dependent deflections over the retention periods. The topography of these waves suggested an involvement of modality-specific sensory storage regions. Spectral analysis has yielded information about the temporal dynamics of auditory working memory processing of individual stimuli, showing activation peaks during the delay phase whose timing was related to task performance. Coherence at different frequencies was enhanced between frontal and sensory cortex. In summary, auditory working memory seems to rely on the dynamic interplay between frontal executive systems and sensory representation regions.